Abiraterone

Prostate Cancer Treatment

Abiraterone is used to treat two primary forms of advanced prostate cancer in men:

• Metastatic castration-resistant prostate cancer: This is prostate cancer that has spread to other areas of the body and no longer responds to medical or surgical treatments intended to lower testosterone levels.
• Metastatic high-risk castration-sensitive prostate cancer: This refers to prostate cancer that has spread to other parts of the body but still responds to hormone therapy.

Abiraterone is not used as a standalone therapy. It must be taken in combination with a corticosteroid medication, such as prednisone or methylprednisolone. This combination is used to help manage the cancer while reducing the risk of certain side effects.

This treatment may be prescribed for patients who have already received chemotherapy or for those who have not yet undergone chemotherapy for their advanced condition.

Mechanism of Action

Abiraterone belongs to a group of medicines known as androgen biosynthesis inhibitors. It works by reducing the production of male hormones, such as testosterone, which prostate cancer cells often need to grow and spread.

Targeting the CYP17 Enzyme

The medication specifically targets and blocks an enzyme called CYP17. This enzyme is a critical part of the process the body uses to create androgens. By inhibiting this enzyme, abiraterone significantly lowers the amount of these hormones available to the cancer cells.

Unlike some other hormone therapies, abiraterone stops hormone production in three different areas of the body:

• The testes: The primary source of male hormones.
• The adrenal glands: Small glands that produce various hormones.
• Prostate cancer cells: The tumor itself can sometimes produce its own hormones to fuel growth.

Combination Therapy

Because blocking the CYP17 enzyme also interferes with the production of other vital hormones like cortisol, abiraterone must be taken with a corticosteroid. This helps maintain the body's hormone balance and prevents certain side effects that could occur if cortisol levels become too low.

Common Side Effects

Many people taking abiraterone experience mild to moderate side effects. These may include:

• Joint swelling or pain
• Muscle aches
• Hot flashes
• Diarrhea
• Cough
• Headache
• Fatigue or weakness
• Nausea or vomiting
• Heartburn
• Difficulty falling or staying asleep

Serious Side Effects

Some side effects can be serious and require immediate medical attention. Contact a healthcare provider if you experience:

• Signs of high blood pressure, such as severe headache or blurred vision
• Signs of low potassium, such as muscle weakness, leg cramps, or an irregular heartbeat
• Swelling in the hands, ankles, or feet (fluid retention)
• Shortness of breath
• Signs of liver problems, including yellowing of the skin or eyes, dark urine, or severe nausea
• Signs of adrenal insufficiency, such as dizziness, lightheadedness, or weight loss
• Rapid or irregular heartbeat
• Bone fractures

Liver Toxicity

Severe liver damage and liver failure have been reported with abiraterone use. Healthcare providers typically monitor liver function through blood tests, specifically measuring ALT, AST, and bilirubin levels, before starting treatment and at regular intervals during therapy. Treatment may need to be interrupted, adjusted, or permanently stopped if liver enzymes become significantly elevated.

Mineralocorticoid Excess

Abiraterone can cause high blood pressure (hypertension), low potassium levels (hypokalemia), and fluid retention (edema). These conditions occur because the medication can increase the levels of certain hormones in the body. Healthcare providers monitor blood pressure and potassium levels at least once a month during treatment. This medication should be used with caution in individuals with a history of heart failure, recent heart attack, or other cardiovascular conditions.

Adrenal Insufficiency

Adrenal insufficiency may occur, particularly if the required corticosteroid (such as prednisone or prednisolone) is stopped suddenly, the dose is reduced, or if the body is under physical stress from infection or injury. Healthcare providers may need to increase the corticosteroid dose during periods of stress. Symptoms of adrenal insufficiency can include dizziness, confusion, or muscle weakness.

Reproductive Risks and Handling

Abiraterone is not indicated for use in women and can cause fetal harm if a pregnant woman is exposed. Pregnant women or those who may become pregnant should not handle abiraterone tablets without protection, such as gloves, because the medication can be absorbed through the skin. Men with female partners of reproductive potential must use effective contraception during treatment and for three weeks after the final dose.

Blood Sugar and Bone Health

The medication may affect blood sugar levels in patients with diabetes, requiring more frequent monitoring of glucose levels. Additionally, long-term use of medications that suppress male hormones may contribute to decreased bone density.

Pregnancy and Handling Precautions

Abiraterone is not indicated for use in women. It is known to cause fetal harm and potential pregnancy loss. Because the drug can be absorbed through the skin, women who are pregnant or who may become pregnant should avoid touching the tablets. If handling is required, gloves should be worn, especially if the tablets are crushed or broken.

Contraception for Men

Men who are taking abiraterone and have female partners of reproductive potential should use effective birth control to prevent pregnancy. Guidelines include:

• Using a condom along with another effective form of contraception during treatment.
• Continuing to use these methods for at least three weeks after the final dose of the medication.

Breastfeeding and Fertility

It is not known whether abiraterone passes into human breast milk, as the medication is not used in females. Regarding fertility, animal studies have shown that the drug may decrease male fertility. Men who have concerns about their fertility should speak with a healthcare professional before starting treatment.

Available Forms

Abiraterone is available in the following oral forms:

• Tablets: Standard abiraterone acetate tablets.
• Micronized Tablets: A specific formulation of abiraterone acetate that uses different technology for absorption.
• Combination Tablets: A single tablet that contains both abiraterone acetate and other active medications.

Standard tablets and micronized tablets are not equivalent and cannot be substituted for one another. These different forms have different administration requirements, particularly regarding food intake.

FDA Approval History

The U.S. Food and Drug Administration (FDA) first approved abiraterone acetate in 2011. It was initially authorized for patients with metastatic castration-resistant prostate cancer who had previously received chemotherapy. Its use was later expanded to include patients who had not yet received chemotherapy and those with metastatic high-risk castration-sensitive prostate cancer.

Approved Indications

Abiraterone is currently approved for the treatment of:

• Metastatic castration-resistant prostate cancer (mCRPC).
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC).

In 2023, the FDA also approved a combination of niraparib and abiraterone acetate, administered with prednisone, for the treatment of adults with BRCA-mutated metastatic castration-resistant prostate cancer.

Regulatory Requirements and Formulations

Abiraterone is available in two main forms: standard abiraterone acetate and a micronized version. These formulations are not interchangeable because they have different dosing requirements and absorption rates. Both forms must be administered in combination with a corticosteroid, such as prednisone or methylprednisolone, to help manage potential side effects related to hormone changes.

There are currently no Boxed Warnings or Risk Evaluation and Mitigation Strategies (REMS) programs required for this medication, though the FDA requires specific monitoring for liver function, blood pressure, and potassium levels during treatment.

Factors Affecting Cost

Several factors influence the out-of-pocket cost for abiraterone:

• Generic vs. Brand Name: Abiraterone is available as a generic medication, which is typically significantly less expensive than brand-name versions such as Zytiga or Yonsa.
• Formulation Type: Standard abiraterone acetate and micronized abiraterone acetate (Yonsa) are different formulations. Because they are not milligram-for-milligram equivalents, their costs and insurance coverage tiers may differ.
• Insurance Coverage: Most Medicare Part D and commercial insurance plans provide coverage for abiraterone, but it is often placed on a higher specialty tier, which may require a significant copayment or coinsurance.

Financial Assistance

For patients who have difficulty affording the medication, options may include:

• Patient Assistance Programs: Some pharmaceutical manufacturers offer programs to provide medications at a lower cost or for free to eligible individuals without insurance or with limited coverage.
• Copay Cards: Manufacturers of brand-name formulations may offer savings cards to help reduce out-of-pocket costs for patients with commercial insurance.

Because abiraterone is a specialty medication, it is often dispensed through specialty pharmacies rather than standard retail locations. Patients should check with their insurance provider and specialty pharmacy to determine the exact cost under their specific plan.